Symptomatic gastroesophageal (GE) reflux is the most common clinical malady which involves the esophagus. Current evidence suggests that GE reflux disease is a multifactorial process governed by: (1) frequency of GE reflux, (2) efficacy of esophageal clearance, (3) potency and volume of refluxed material, and (4) resistance of the esophageal mucosa to injury. Our aim is this study is to perform an indepth investigation of the first two factors. Namely, we plan to evaluate the mechanisms governing GE reflux and esophageal clearance in normal volunteers and patients with reflux symptoms. A major thrust in this investigation will be utilization of a research model which permits overnight monitoring in human subjects of: (1) motor activity in the stomach, lower esophageal sphincter (LES), esophageal body, and pharynx by manometry, (2) esophageal pH by an intraluminal electrode, and (3) continuous recording of electrical patterns of wakefullness and sleep by EEG. Reliable continuous recording of LES pressure is now made possible by an infused sleeve device which straddles the sphincter. Preliminary studies using this model suggest that in normal subjects: (1) reflux is related to transient, inappropriate LES relaxation, rather than to unduly low basal LES pressure, and (2) esophageal clearance is effected mainly by swallow-induced primary peristalsis rather than by secondary peristalsis. Studies in several patients with reflux esophagitis, suggest that mechanisms similar to those shown in volunteers may apply to at least some patients with symptomatic GE reflux. We will also do short-interval studies, 2 to 4 hours in length, monitoring esophageal-body motor activity, GE reflux, and esophageal acid clearance. In certain studies, a radioisotope scintiscan method will be used to quantitate GE reflux and esophageal clearance. During some of the studies pharmacologic depression or enhancement of LES pressure and esophageal body motor activity will provide additional information on the mechanisms of GE reflux and esophageal clearance. Lastly, we will determine the effects of medical and surgical therapy on the incidence of GE reflux and the efficacy of esophageal clearance.